| First Author | Sikandar SS | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 45 | Pages | eabm3548 |
| PubMed ID | 36351009 | Mgi Jnum | J:380167 |
| Mgi Id | MGI:8279138 | Doi | 10.1126/sciadv.abm3548 |
| Citation | Sikandar SS, et al. (2022) Identification of a minority population of LMO2(+) breast cancer cells that integrate into the vasculature and initiate metastasis. Sci Adv 8(45):eabm3548 |
| abstractText | Metastasis is responsible for most breast cancer-related deaths; however, identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immature THY1(+)/VEGFA(+) tumor epithelial cells in human breast tumor biopsies that display angiogenic features and are marked by the expression of the oncogene, LMO2. Higher abundance of LMO2(+) basal cells correlated with tumor endothelial content and predicted poor distant recurrence-free survival in patients. Using MMTV-PyMT/Lmo2(CreERT2) mice, we demonstrated that Lmo2 lineage-traced cells integrate into the vasculature and have a higher propensity to metastasize. LMO2 knockdown in human breast tumors reduced lung metastasis by impairing intravasation, leading to a reduced frequency of circulating tumor cells. Mechanistically, we find that LMO2 binds to STAT3 and is required for STAT3 activation by tumor necrosis factor-alpha and interleukin-6. Collectively, our study identifies a population of metastasis-initiating cells with angiogenic features and establishes the LMO2-STAT3 signaling axis as a therapeutic target in breast cancer metastasis. |
